1. Field of the Invention
The present invention relates to novel isoxazolidinedione derivatives. More particularly, the present invention relates to novel isoxazolidinedione derivatives which have hypoglycemic action and hypolipidemic action, and are useful as therapeutic agents for diabetes and the complications thereof, and as therapeutic agents for the related diseases such as hyperlipidema.
2. Description of Related Art
In general, the treatment of non-insulin-dependent diabetes mellitus (NIDDM) involves a combination of alimentotherapy, kinesitherapy, and administration of insulin or oral hypoglycemic agents. As the oral hypoglycemic agents, there are currently known sulfonylureas such as tolbutamide, chlorpropamide, acetohexamide, glibenclamide and tolazamide and biguanides such as phenformin, buformin and metformin.
While the sulfonylureas have strong hypoglycemic action, they sometimes induce severe and prolonged hypoglycemia, and chronic use thereof may impair their effectiveness. In addition, the biguanides frequently induce severe lactic acidosis. For these reasons, the use of these medications has required considerable attention.
Japanese Patent Unexamined Publication No. 85372/1988 corresponding to U.S. Pat. No. 4,572,912 teaches that thiazolidinedione derivatives such as 5-4-2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy!benzyl!-2,4-thiazolidinedion e! have hypoglycemic action, and Japanese Patent Unexamined Publication No. 51189/1985 corresponding to U.S. Pat. No. 4,572,912 teaches that thiazolidinedione derivatives such as (.+-.)-5-4-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)benzyl!-2, 4-thiazolidinedione! have hypoglycemic action. It has been also taught that oxazolidinedione derivatives such as 5-4-2-(2-phenyl-5-methyloxazol-4-yl)ethoxy!benzyl!-2,4-oxazolidinedione ! described in Japanese Patent Unexamined Publication No. 170478/1991 corresponding to U.S. Pat No. 5,498,621 and 5-4-2-N-(2-benzoxazolyl)-N-methyl!amino-ethoxy!benzyl!-2,4-oxazolidine dione! described in W092/02520 corresponding to U.S. Pat. No. 5,391,565 possess hypoglycemic action and cholesterol lowering action.
However, these compounds are not necessarily satisfactory in terms of activity, and the use thereof rather causes anxiety when their side effects (e.g. toxicity) are taken into consideration. These publications do not include a description suggesting an isoxazolidinedione derivative such as the compounds of the present invention.